PEX3

peroxisomal biogenesis factor 3, the group of Peroxins

Basic information

Region (hg38): 6:143450805-143490616

Links

ENSG00000034693 ∙ NCBI:8504 ∙ OMIM:603164 ∙ HGNC:8858 ∙ Uniprot:P56589 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peroxisome biogenesis disorder 10A (Zellweger) (Moderate), mode of inheritance: AR
• Zellweger spectrum disorders (Supportive), mode of inheritance: AR
• peroxisome biogenesis disorder 10A (Zellweger) (Strong), mode of inheritance: AR
• peroxisome biogenesis disorder (Definitive), mode of inheritance: AR
• peroxisome biogenesis disorder 10B (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peroxisome biogenesis factor disorder 3; Peroxisome biogenesis disorder 10A (Zellweger); Peroxisome biogenesis disorder 10B	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal	10968777; 10679269; 10942428; 27557811

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PEX3 gene.

• not provided (13 variants)
• Peroxisome biogenesis disorder 10A (Zellweger) (2 variants)
• Peroxisome biogenesis disorder (1 variants)
• Peroxisome biogenesis disorder 1A (Zellweger) (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PEX3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	56	2	61
missense		2	117	2		121
nonsense	6	3	1			10
start loss		1				1
frameshift	6					6
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	5	1			7
splice region	1		14	17		32
non coding			29	64	28	121
Total	13	11	152	122	30

Highest pathogenic variant AF is 0.0000132

Variants in PEX3

This is a list of pathogenic ClinVar variants found in the PEX3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-143450812-G-C		Peroxisome biogenesis disorder 10A (Zellweger)	Uncertain significance (Jan 13, 2018)
6-143450829-G-C		Peroxisome biogenesis disorder 10A (Zellweger)	Uncertain significance (Jan 13, 2018)
6-143450846-T-C		Peroxisome biogenesis disorder 10A (Zellweger)	Benign (Jan 13, 2018)
6-143450857-C-T		Peroxisome biogenesis disorder 10A (Zellweger)	Uncertain significance (Jan 13, 2018)
6-143450867-C-CG		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Jun 14, 2016)
6-143450868-G-C		Peroxisome biogenesis disorder 10A (Zellweger)	Uncertain significance (Jan 12, 2018)
6-143450891-G-GTC		Peroxisome biogenesis disorder 1A (Zellweger)	Uncertain significance (Jun 14, 2016)
6-143450947-G-T		Peroxisome biogenesis disorder 10A (Zellweger)	Uncertain significance (Jan 13, 2018)
6-143451036-CCTAAAGATGCTGAGGT-C		Peroxisome biogenesis disorder 10B;Peroxisome biogenesis disorder 10A (Zellweger)	Likely pathogenic (Jan 09, 2024)
6-143451039-A-G		not specified • Peroxisome biogenesis disorder 10A (Zellweger)	Benign/Likely benign (Jan 13, 2018)
6-143451058-T-A			Uncertain significance (Nov 03, 2021)
6-143451058-T-C		Peroxisome biogenesis disorder 10B	Uncertain significance (Nov 05, 2019)
6-143451059-G-A		Peroxisome biogenesis disorder	Pathogenic (Nov 20, 2023)
6-143451062-A-G			Uncertain significance (Apr 06, 2022)
6-143451068-T-A			Uncertain significance (Jul 13, 2022)
6-143451070-A-C			Uncertain significance (Jul 06, 2022)
6-143451093-C-T		Peroxisome biogenesis disorder 10A (Zellweger)	Conflicting classifications of pathogenicity (Jun 23, 2024)
6-143451096-C-T		PEX3-related disorder	Likely benign (Dec 28, 2022)
6-143451099-G-C			Likely benign (May 03, 2023)
6-143451104-C-T			Uncertain significance (Feb 20, 2022)
6-143451112-G-A			Uncertain significance (Jul 17, 2023)
6-143451127-C-T			Likely benign (May 04, 2021)
6-143451128-G-A			Likely benign (Jan 29, 2024)
6-143451132-T-C			Likely benign (Jul 05, 2022)
6-143451174-C-T			Benign (Sep 11, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PEX3	protein_coding	protein_coding	ENST00000367591	12	39204

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0163	0.983	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	145	191	0.759	0.00000890	2439
Missense in Polyphen		37	64.308	0.57536		846
Synonymous	0.703	60	67.3	0.891	0.00000317	695
Loss of Function	3.26	8	25.9	0.309	0.00000153	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000265	0.000265
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000971	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes. {ECO:0000269|PubMed:10848631, ECO:0000269|PubMed:15007061}.
• Disease: DISEASE: Peroxisome biogenesis disorder 10A (PBD10A) [MIM:614882]: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. {ECO:0000269|PubMed:10848631, ECO:0000269|PubMed:10958759}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peroxisome biogenesis disorder 10B (PBD10B) [MIM:617370]: A moderately severe peroxisome biogenesis disorder belonging to the Zellweger disease spectrum. PBD10B is characterized by neonatal jaundice, dysmorphic features, delayed psychomotor development, axial hypotonia that can progress to severe spastic paraparesis with hyperreflexia, nephrocalcinosis, neurogenic bladder, nystagmus, and cataracts. Laboratory studies show increased levels of very long-chain fatty acids. Inheritance is autosomal recessive. {ECO:0000269|PubMed:27557811}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Peroxisome - Homo sapiens (human);ABC transporters in lipid homeostasis;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

• pRec: 0.249

Intolerance Scores

• loftool: 0.593
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.12

Haploinsufficiency Scores

• pHI: 0.331
• hipred: Y
• hipred_score: 0.622
• ghis: 0.626

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pex3
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; limbs/digits/tail phenotype; hematopoietic system phenotype; skeleton phenotype; vision/eye phenotype

Gene ontology

• Biological process: peroxisome organization;peroxisome membrane biogenesis;protein import into peroxisome membrane;transmembrane transport
• Cellular component: nucleoplasm;peroxisome;peroxisomal membrane;integral component of peroxisomal membrane;endoplasmic reticulum;cytosol;membrane;protein-containing complex;protein-lipid complex
• Molecular function: protein binding;lipid binding;protein binding, bridging;protein dimerization activity